In Search of a Better Approach to Breast Cancer Screening

As a venture investor in the healthcare sector, I see a lot of new medical technologies that promise improvement over the current standard of care. Opportunities that represent truly transformational change in medicine are rare, and those that address a major clinical challenge affecting tens of millions of lives are rarer still.

Breast cancer screening is one of those areas, and increased attention is focused on the inadequacy of mammography and other diagnostic tests currently used for a large population of at-risk women.

Many people will be affected by breast cancer in their lifetime, if not directly then through a close family member or friend who gets diagnosed with the disease. The statistics involving breast cancer are sobering: it is the most commonly diagnosed cancer among American women after skin cancer, and the number two cause of cancer-related deaths in women after lung cancer. It affects about 1 in 8 women over the course of their lifetime. Approximately 300,000 women in the U.S. will be diagnosed with breast cancer this year, and an estimated 40,000 died in 2014 from this disease.

One fact that’s not well known is that approximately half of all women have what doctors call “dense breasts.” Dense breasts have more connective/glandular tissue as compared with breasts that have more fatty tissue. Breast density can mask the detection of cancer through traditional screening techniques, and this problem has long frustrated physicians. When a woman has a routine mammogram, the radiologist is generally looking for something that appears white in the image (a mass or architectural distortion) against a mostly dark background. This is relatively easy to see in women with predominantly fatty breast tissue. However, for women with dense breast tissue, most of the image appears white. Trying to spot a cancer with mammography in these women is like trying to find a snowball in a snowstorm.

Breast density has also been found to increase cancer risk independently of this masking problem. Studies suggest the relative cancer risk for dense breast is as much as 4-5 times higher versus non-dense breast women. Mammography is a test that does a very poor job finding cancer in the same group of women for whom risk of breast cancer is elevated. Improvements to mammography and ultrasound approaches over the years for dense breast have been incremental at best; perhaps one additional cancer detected for every 1,000 women screened. Meanwhile, roughly two-thirds of tumors in these women still go undetected until they grow larger and later-stage, when they are more challenging and expensive to treat.

These relatively small improvements in cancer detection come at the cost of an unacceptably high level of false findings. One recent study showed that nearly 95 percent of all biopsies indicated by an ultrasound exam came back benign. This may ultimately be a great relief to the many women who live for weeks, or even months, in fear of a different diagnosis after a suspicious finding. But it’s easy to see how the shortcomings of existing technologies for breast screening extract a significant physical, emotional, and economic cost.

The reality is that we need a better way.

There are still far too many women who are diagnosed with invasive cancers that could have been caught much earlier through improved screening. Women with dense breasts would benefit from a technology with superior sensitivity like MRI, which is occasionally used in screening but is too costly and impractical for use as a tool for all but the highest-risk women. There are also far too many false positive findings, including with MRI, which lead to unnecessary follow-up tests and biopsies. We need a technology with much better specificity—meaning if you see something suspicious, it is likely cancer. Finally, any acceptable approach must have a near 100 percent negative predictive value—meaning if you don’t see something, then it’s not there.

A newly developed technique called Molecular Breast Imaging (MBI) addresses this need, and is being commercialized by companies like Gamma Medica (a Psilos portfolio company) and GE Healthcare. MBI sees through tissue density and highlights tumors that are often hidden with mammography. This promising new technology has been shown to increase cancer detection in women with dense breast by nearly 4 times, versus the roughly 30-35 percent improvement that tomography and ultrasound have demonstrated. Further, MBI studies have shown equivalent sensitivity to MRI (around 91 percent) at a fraction of the cost while significantly improving specificity (93 percent), and near-perfect negative predictive value, which leads to far fewer unnecessary follow-on tests and biopsies.

While MBI appears to be the silver bullet that addresses the shortcomings of mammography and ultrasound, it is still at the early stages of clinical adoption. This may be about to change through the recent passage of dense breast notification laws in 19 states (and more to come), as well as federal legislation that has strong bipartisan support. Under these new laws, millions of women will start learning about their breast density and the risk of relying on routine mammograms to detect cancer at its earliest stages.

For now, doctors generally view this legislation as an unwelcome disruption to the way they have dealt with breast screening from a workflow standpoint. Surely they want to provide the very best care for their patients, but they’ll also have to contend with lots of newly informed women coming back to them with questions and concerns about their annual mammogram—and ultimately demanding better answers. I believe in time, this will be viewed more as an opportunity. With new game-changing technologies like MBI and others, radiologists will now have a much better array of tools to deliver a more personalized approach to breast screening, leading to faster, more confident diagnoses and ultimately many more lives saved.

David Eichler is a Managing Member of Psilos Group and focuses on investments in the healthcare services, healthcare IT, and medical technology sectors. He currently serves as Chairman of Gamma Medica, Inc. Follow @PsilosGroup

Dr. McGinty – You raise an important issue with respect to radiation dose. The article you cited in your comment relates to an older version of the technology (BSGI), as well as a different technique involving PET for breast imaging (PEM). MBI has advanced considerably since BSGI and is now being performed at doses as low as 4 millicuries — or around 1/5 that of BSGI. The image quality for MBI relative to BSGI is also significantly better. Additional technology improvements will enable MBI to be done at ~2 mCi, which is nearly equivalent to the radiation dose received from mammo/tomo screening.

There seems to be something missing in this article. Yes, doctors can be slow to adopt new treatments and technologies. If the technology works as well as described above, then its use would seem to be a no-brainer. If that’s the case, why is legislation needed to inform women that they have dense breasts? What is the purpose of the new legislation? One would think that the marketplace would be rushing to adopt this new methodology, and I see a big warning flag if legislation is required to drive its adoption. Can you tell me what the cost is of the MBI scan compared to conventional mammography? Compared to conventional mammography, how many women would need to be switched over to MBI in order to detect one new breast cancer? In that same group, how many more women will develop other cancers due to the higher radiation dosage compared to mammography? I’d feel a lot better knowing that the legislation mentioned in the article is not being pushed by lobbyists hired by the companies that want to see this technology expand to drive their profits. Can you confirm that’s not the case?

Dr. Lyman – thank you for your comment. In response to your questions:

1) I can confirm that Gamma Medica has not hired any lobbyists to push legislation! Credit for the wave of dense breast notification laws is actually due to a woman named Nancy Cappello who formed an advocacy group called Are You Dense. In 2004, Dr. Cappello was diagnosed with stage 3 invasive breast cancer just 2 months after receiving a normal mammogram report. The 2.5cm tumor was completely missed by mammography because of her breast density. I encourage you to learn more about Nancy’s story and the Are You Dense organization here: http://areyoudense.com/

2) The average reimbursement for MBI is currently around $380; more expensive than screening mammography which is reimbursed at an average of $155 per scan. However, the economic ROI for payors with MBI is evident when looking at the total cost of breast cancer screening which may include any or all of the following: repeat mammos, ultrasounds, MRIs and/or biopsies. There is an actuarial study by Milliman that details the costs of breast cancer screening you may find interesting here: http://us.milliman.com/uploadedFiles/insight/2014/actuarial-analysis-breast-cancer-screening.pdf

In this article, Mayo Clinic concluded that at the new lower dose, the benefit-risk ratio for MBI in women aged 40-80 with dense breast is 46:1 (i.e., 46 cancer deaths reduced for each one cancer caused by low-dose MBI).